Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.

Detalhes bibliográficos
Autor(a) principal: Ersoy, Selvi C.
Data de Publicação: 2022
Outros Autores: Gonçalves, Bárbara, Cavaco, Gonçalo, Manna, Adhar C., Sobral, Rita G, Nast, Cynthia C., Proctor, Richard A., Chambers, Henry F., Cheung, Ambrose, Bayer, Arnold S
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/146097
Resumo: grant from the National Institutes of Health:1RO1-AI146078 (to A.S.B.). LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB.
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spelling Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.methicillin-resistant Staphylococcus aureus (MRSA),sodium bicarbonatepenicillin-binding proteins (PBPs)peptidoglycan (PG)wall teichoic acid (WTA)lactamsmethicillin resistancegrant from the National Institutes of Health:1RO1-AI146078 (to A.S.B.). LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB.Methicillin-resistant Staphylococcus aureus (MRSA) strains pose major treatment challenges due to their innate resistance to most β-lactams under standard in vitro antimicrobial susceptibility testing conditions. A novel phenotype among MRSA, termed "NaHCO 3 responsiveness," where certain strains display increased susceptibility to β-lactams in the presence of NaHCO 3, has been identified among a relatively large proportion of MRSA isolates. One underlying mechanism of NaHCO 3 responsiveness appears to be related to decreased expression and altered functionality of several genes and proteins involved in cell wall synthesis and maturation. Here, we studied the impact of NaHCO 3 on wall teichoic acid (WTA) synthesis, a process intimately linked to peptidoglycan (PG) synthesis and functionality, in NaHCO 3-responsive versus -nonresponsive MRSA isolates. NaHCO 3 sensitized responsive MRSA strains to cefuroxime, a specific penicillin-binding protein 2 (PBP2)-inhibitory β-lactam known to synergize with early WTA synthesis inhibitors (e.g., ticlopidine). Combining cefuroxime with ticlopidine with or without NaHCO 3 suggested that these latter two agents target the same step in WTA synthesis. Further, NaHCO 3 decreased the abundance and molecular weight of WTA only in responsive strains. Additionally, NaHCO 3 stimulated increased autolysis and aberrant cell division in responsive strains, two phenotypes associated with disruption of WTA synthesis. Of note, studies of key genes involved in the WTA biosynthetic pathway (e.g., tarO, tarG, dltA, and fmtA) indicated that the inhibitory impact of NaHCO 3 on WTA biosynthesis in responsive strains likely occurred posttranslationally. IMPORTANCE MRSA is generally viewed as resistant to standard β-lactam antibiotics. However, a NaHCO 3-responsive phenotype is observed in a substantial proportion of clinical MRSA strains in vitro, i.e., isolates which demonstrate enhanced susceptibility to standard β-lactam antibiotics (e.g., oxacillin) in the presence of NaHCO 3. This phenotype correlates with increased MRSA clearance in vivo by standard β-lactam antibiotics, suggesting that patients with infections caused by such MRSA strains might be amenable to treatment with β-lactams. The mechanism(s) behind this phenotype is not fully understood but appears to involve mecA-PBP2a production and maturation axes. Our study adds significantly to this body of knowledge in terms of additional mechanistic targets of NaHCO 3 in selected MRSA strains. This investigation demonstrates that NaHCO 3 has direct impacts on S. aureus wall teichoic acid biosynthesis in NaHCO 3-responsive MRSA. These findings provide an additional target for new agents being designed to synergistically kill MRSA using β-lactam antibiotics.DCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitRUNErsoy, Selvi C.Gonçalves, BárbaraCavaco, GonçaloManna, Adhar C.Sobral, Rita GNast, Cynthia C.Proctor, Richard A.Chambers, Henry F.Cheung, AmbroseBayer, Arnold S2022-12-09T22:15:26Z2022-11-152022-11-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article14application/pdfhttp://hdl.handle.net/10362/146097eng2165-0497PURE: 47879302https://doi.org/10.1128/spectrum.03422-22info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:27:04Zoai:run.unl.pt:10362/146097Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:52:28.538470Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.
title Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.
spellingShingle Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.
Ersoy, Selvi C.
methicillin-resistant Staphylococcus aureus (MRSA),
sodium bicarbonate
penicillin-binding proteins (PBPs)
peptidoglycan (PG)
wall teichoic acid (WTA)
lactams
methicillin resistance
title_short Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.
title_full Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.
title_fullStr Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.
title_full_unstemmed Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.
title_sort Influence of Sodium Bicarbonate on Wall Teichoic Acid Synthesis and β-Lactam Sensitization in NaHCO 3-Responsive and Nonresponsive Methicillin-Resistant Staphylococcus aureus.
author Ersoy, Selvi C.
author_facet Ersoy, Selvi C.
Gonçalves, Bárbara
Cavaco, Gonçalo
Manna, Adhar C.
Sobral, Rita G
Nast, Cynthia C.
Proctor, Richard A.
Chambers, Henry F.
Cheung, Ambrose
Bayer, Arnold S
author_role author
author2 Gonçalves, Bárbara
Cavaco, Gonçalo
Manna, Adhar C.
Sobral, Rita G
Nast, Cynthia C.
Proctor, Richard A.
Chambers, Henry F.
Cheung, Ambrose
Bayer, Arnold S
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv DCV - Departamento de Ciências da Vida
UCIBIO - Applied Molecular Biosciences Unit
RUN
dc.contributor.author.fl_str_mv Ersoy, Selvi C.
Gonçalves, Bárbara
Cavaco, Gonçalo
Manna, Adhar C.
Sobral, Rita G
Nast, Cynthia C.
Proctor, Richard A.
Chambers, Henry F.
Cheung, Ambrose
Bayer, Arnold S
dc.subject.por.fl_str_mv methicillin-resistant Staphylococcus aureus (MRSA),
sodium bicarbonate
penicillin-binding proteins (PBPs)
peptidoglycan (PG)
wall teichoic acid (WTA)
lactams
methicillin resistance
topic methicillin-resistant Staphylococcus aureus (MRSA),
sodium bicarbonate
penicillin-binding proteins (PBPs)
peptidoglycan (PG)
wall teichoic acid (WTA)
lactams
methicillin resistance
description grant from the National Institutes of Health:1RO1-AI146078 (to A.S.B.). LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB.
publishDate 2022
dc.date.none.fl_str_mv 2022-12-09T22:15:26Z
2022-11-15
2022-11-15T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/146097
url http://hdl.handle.net/10362/146097
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2165-0497
PURE: 47879302
https://doi.org/10.1128/spectrum.03422-22
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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